Soluble striatal extracts enhance development of mesencephalic dopaminergic neurons in vitro

Recent studies have suggested that diffusible factors released by neural target tissues enhance survival, growth, and differentiation of neurons within the central, as well as the peripheral, nervous system. In this report, we use catecholamine cytofluorescence to demonstrate that a soluble factor from the striatum produces a 4-fold increase in number of catecholamine cytofluorescent-positive dopaminergic neurons in dissociated mesencephalon cultures prepared from embryonic 14-day-old rats. The same soluble extract enhances the number of neurites per cell and the length of neurites, and also produces a greater than 3.5-fold stimulation of high affinity dopamine uptake into neurons. Such stimulation is significantly reduced following trypsin treatment. The trophic effects on dopaminergic neurons are maximal in extracts of the striatum, but are also found in extracts of the hippocampus-entorhinal cortex-amygdaloid nucleus and the cerebral cortex, although they are less in extracts of the cerebellum, negligible in the olfactory bulb, and absent in the liver. With molecular sieving chromatography, the soluble factors stimulating high affinity dopamine uptake are partially separable from the factors stimulating neuronal high affinity GABA uptake. The approximate molecular weight of the factors influencing dopaminergic neurons is 1500-2200 Da.